Mendelian randomisation analyses of UK Biobank and published data suggest that increased adiposity lowers risk of breast and prostate cancer

Abstract

Breast (BCa) and prostate (PrCa) cancer are the first and second most common types of cancer in women and men, respectively. We aimed to explore the causal effect of adiposity on BCa and PrCa risk in the UK Biobank and published data. We used Mendelian randomisation (MR) to assess the causal effect of body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on BCa and PrCa risk. We found that increased BMI, WC and HC decreased the risk of breast cancer (OR 0.70 per 5.14 kg/m² [0.59-0.85, p = 2.1 × 10^-4], 0.76 per 12.49 cm [60-0.97, p = 0.028] and 0.73 per 10.31 cm [0.59-0.90, p = 3.7 × 10^-3], respectively) and increased WC and BMI decreased the risk of prostate cancer (0.68 per 11.32 cm [0.50-0.91, p = 0.01] and 0.76 per 10.23 kg/m² [0.61-0.95, p = 0.015], respectively) in UK Biobank participants. We confirmed our results with a two-sample-MR of published data. In conclusion, our results suggest a protective effect of adiposity on the risk of BCa and PrCa highlighting the need to re-evaluate the role of adiposity as cancer risk factor.